Role of recombinant plasmid pEGFP-N1-IGF-1 transfection in alleviating osteoporosis in ovariectomized rats

Decreased levels of serum insulin-like growth factor-1 (IGF-1) have been proven to cause osteoporosis. Gene transfer of IGF-1 offers an attractive technology to treat skeletal metabolic disorders including osteoporosis, but the viral vectors are limited by their high antigenicity and immune response...

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Veröffentlicht in:Journal of molecular histology 2013-10, Vol.44 (5), p.535-544
Hauptverfasser: Liu, Hai Chun, Zhao, Hua, Chen, Jian, Wu, Wen Liang, Wang, Hong Liang, Jiao, Gang Jun, Chen, Yun Zhen
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container_end_page 544
container_issue 5
container_start_page 535
container_title Journal of molecular histology
container_volume 44
creator Liu, Hai Chun
Zhao, Hua
Chen, Jian
Wu, Wen Liang
Wang, Hong Liang
Jiao, Gang Jun
Chen, Yun Zhen
description Decreased levels of serum insulin-like growth factor-1 (IGF-1) have been proven to cause osteoporosis. Gene transfer of IGF-1 offers an attractive technology to treat skeletal metabolic disorders including osteoporosis, but the viral vectors are limited by their high antigenicity and immune response. Our purpose was to investigate the expression of a non-invasive vector, recombinant plasmid enhanced green fluorescent protein-N1 (pEGFP-N1) that transferred IGF-1 gene into ovariectomized (OVX) rats in vivo and evaluate the effect of this therapy on osteoporosis. OVX or sham operations were performed in 60 female, 7-month-old unmated SD rats. 12 weeks after OVX operation, the vectors were transfected to the 10-month-old rats and experimental data were detected from 48 h to 7 week after transfection. Our results showed that remarkable expression of fluorescence and serum IGF-1 was observed in the rats transfected by recombinant plasmids, indicating that IGF-1 gene was successfully transferred to OVX rats by injecting the vector through hydrodynamic method via the tail vein. The bone metabolism index including serum alkaline phosphatase, the histomorphometric parameters of lumbar vertebra including trabecular area percentage, trabecular thickness, trabecular number and trabecular separation, and the bone mineral density (BMD) and biomechanical parameters of lumbar vertebra including BMD, maximum condensing force, crushing strength in OVX rats transfected by pEGFP-N1-IGF-1 were improved remarkably compared with OVX+pEGFP-N1 rats, indicating that the transfection of recombinant plasmid pEGFP-N1-IGF-1 played a significant role in alleviating osteoporosis in rats induced by OVX. This encouraged a potential approach of IGF-1 gene therapy to the treatment of osteoporosis.
doi_str_mv 10.1007/s10735-013-9498-3
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Gene transfer of IGF-1 offers an attractive technology to treat skeletal metabolic disorders including osteoporosis, but the viral vectors are limited by their high antigenicity and immune response. Our purpose was to investigate the expression of a non-invasive vector, recombinant plasmid enhanced green fluorescent protein-N1 (pEGFP-N1) that transferred IGF-1 gene into ovariectomized (OVX) rats in vivo and evaluate the effect of this therapy on osteoporosis. OVX or sham operations were performed in 60 female, 7-month-old unmated SD rats. 12 weeks after OVX operation, the vectors were transfected to the 10-month-old rats and experimental data were detected from 48 h to 7 week after transfection. Our results showed that remarkable expression of fluorescence and serum IGF-1 was observed in the rats transfected by recombinant plasmids, indicating that IGF-1 gene was successfully transferred to OVX rats by injecting the vector through hydrodynamic method via the tail vein. The bone metabolism index including serum alkaline phosphatase, the histomorphometric parameters of lumbar vertebra including trabecular area percentage, trabecular thickness, trabecular number and trabecular separation, and the bone mineral density (BMD) and biomechanical parameters of lumbar vertebra including BMD, maximum condensing force, crushing strength in OVX rats transfected by pEGFP-N1-IGF-1 were improved remarkably compared with OVX+pEGFP-N1 rats, indicating that the transfection of recombinant plasmid pEGFP-N1-IGF-1 played a significant role in alleviating osteoporosis in rats induced by OVX. 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The bone metabolism index including serum alkaline phosphatase, the histomorphometric parameters of lumbar vertebra including trabecular area percentage, trabecular thickness, trabecular number and trabecular separation, and the bone mineral density (BMD) and biomechanical parameters of lumbar vertebra including BMD, maximum condensing force, crushing strength in OVX rats transfected by pEGFP-N1-IGF-1 were improved remarkably compared with OVX+pEGFP-N1 rats, indicating that the transfection of recombinant plasmid pEGFP-N1-IGF-1 played a significant role in alleviating osteoporosis in rats induced by OVX. 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The bone metabolism index including serum alkaline phosphatase, the histomorphometric parameters of lumbar vertebra including trabecular area percentage, trabecular thickness, trabecular number and trabecular separation, and the bone mineral density (BMD) and biomechanical parameters of lumbar vertebra including BMD, maximum condensing force, crushing strength in OVX rats transfected by pEGFP-N1-IGF-1 were improved remarkably compared with OVX+pEGFP-N1 rats, indicating that the transfection of recombinant plasmid pEGFP-N1-IGF-1 played a significant role in alleviating osteoporosis in rats induced by OVX. This encouraged a potential approach of IGF-1 gene therapy to the treatment of osteoporosis.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>23508541</pmid><doi>10.1007/s10735-013-9498-3</doi><tpages>10</tpages></addata></record>
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subjects Alkaline phosphatase
Alkaline Phosphatase - blood
Alkaline Phosphatase - genetics
Animals
Biomedical and Life Sciences
Biomedicine
Bone Density - genetics
Cell Biology
Developmental Biology
Female
Genetic Therapy - methods
Green Fluorescent Proteins - blood
Green Fluorescent Proteins - genetics
Injections, Intravenous
Insulin-Like Growth Factor I - genetics
Insulin-Like Growth Factor I - metabolism
Life Sciences
Lumbar Vertebrae - metabolism
Lumbar Vertebrae - pathology
Original Paper
Osteoporosis - genetics
Osteoporosis - pathology
Osteoporosis - therapy
Ovariectomy
Plasmids
Rats
Rats, Sprague-Dawley
Recombinant Fusion Proteins - blood
Recombinant Fusion Proteins - genetics
Transfection
title Role of recombinant plasmid pEGFP-N1-IGF-1 transfection in alleviating osteoporosis in ovariectomized rats
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